Protein influences regeneration of vascular cells

Date:
August 19, 2020
Source:
University of Bonn
Summary:
Physicians have discovered how the communication between individual
cells can be influenced with the help of a specific protein. These
findings are an important approach to improving the treatment
of diseases such as arteriosclerosis (calcified blood vessels),
which causes heart attacks.



FULL STORY ========================================================================== Through their basic research, physicians at the Heart Center of
the University Hospital Bonn have discovered how the communication
between individual cells can be influenced with the help of a specific
protein. These findings are an important approach to improving the
treatment of diseases such as arteriosclerosis (calcified blood vessels),
which causes heart attacks. The study was published online in advance
in the Journal of Extracellular Vesicles, the printed version will be
published shortly.


==========================================================================
The human body consists of an inconceivably large number of cells. Current scientific studies assume around 40 trillion cells, depending on the
weight and size of the person. Most cells come together to perform their function in the body in the best possible way. Collectively they form
tissue, organs and muscles. The most important requirement for good
cellular interaction is for the cells to communicate with each other as effectively as possible.

"In order for cells to communicate effectively with each other,
they need a postman to carry information from one cell to the next,"
explains Dr. Andreas Zietzer, cardiologist at the Heart Center of Bonn University Hospital. "This is precisely the role played by extracellular vesicles." For a long time, these vesicles were considered to have little biological significance. It was assumed that the vesicles were only used
to get rid of excess proteins and other molecules, making them a kind
of cellular garbage disposal. However, it is now known that vesicles
play a key role in intercellular communication.

Vesicles serve as postmen between the cells The principle of the
vesicles can be explained quite simply: They are released as extremely
small membrane bubbles -- only about two thousandths of a millimeter in
size -- by cells in our body and can then be taken up and utilized by
other cells. Zietzer describes the crucial function of the vesicles "as postmen, they transport various contents and thereby enable the exchange
of information between cells." In addition to proteins and lipids,
this communication process also involves transporting ribonucleic acids
(RNAs). These RNAs are copies of the genetic information and are required
for carrying out its function. The physicians at the University of Bonn concentrated their research primarily on so-called microRNAs, which are responsible for fine tuning the switching on and off of genes.



========================================================================== "Because microRNAs have considerable influence on the biology of the
cells, vesicles can influence the function of recipient cells depending
on their specific cargo," says Zietzer. This is because, depending on
which microRNA is enriched in the vesicles, the information transported
by the vesicles also changes and with it the effect on the recipient
cells that take up the vesicles and their cargo.

"It would be a breakthrough for researchers and physicians if they
could control which information is transported between cells and which
is not," says Zietzer, looking to the future. "However, precisely this
kind of manipulation of cell-to-cell communication has so far been
barely investigated." The research group, led by Dr. Andreas Zietzer,
Dr. Rabiul Hosen and Dr. Felix Jansen (head of the research group),
at the Heart Center of the University Hospital Bonn has now succeeded
in using a new mechanism on human cells to clarify how the sorting of
specific RNAs within the vesicles works. To this end, the researchers
used a mass spectrometer to identify more than 3,000 proteins and 300
microRNAs that were found to be enclosed in the vesicles and ready for transport to other cells.

An RNA-binding protein holds back the mail The three researchers were able
to show that a specific RNA-binding protein (hnRNPU for short) retains
the microRNAs in the donor cell like a sponge, thereby preventing them
from being packed into vesicles and transported to another cell. The
exact opposite is true when this particular protein is switched off:
In this case there is an elevated release of the microRNAs, which are
then increasingly packed into the vesicles.

"The RNA-binding protein hnRNPU therefore assumes the role of a
gatekeeper, deciding which and how many microRNAs are released from
the donor cell for transport to the recipient cell," Andreas Zietzer
summarizes the research results. This function enables the protein hnRNPU
to significantly influence the communication between cells.

These observations hold great therapeutic potential; Zietzer, Hosen and
Jansen were able to show that the transfer of certain microRNAs via
the vesicles can be controlled by increasing or reducing the amount
of hnRNPU in the donor cells. "This enables a targeted release, or
retention, of microRNAs that promote regeneration and thereby positively
or negatively influence the regenerative ability of diseased vascular
cells," comments Zietzer on the potential intervention in cellular communication. Medically, this is of high importance, as the regenerative ability of the vascular cells in calcified vessels (arteriosclerosis)
is already limited in the early stages of the disease.

Zietzer, Hosen, and Jansen now hope to apply their findings on
intercellular communication using extracellular vesicles: "It is, for
instance, conceivable that the targeted local activation or deactivation
of the protein hnRNPU in healthy parts of the vascular system might lead
to a 'swarm' of regeneration- promoting vesicles to be dispatched, which
could then be taken up by already damaged vascular areas and accelerate regeneration there. In critical situations, such as after a heart attack,
this could promote the healing process of patients," says Zietzer about
the concrete benefit of this basic research.

Further applicability studies are in progress. The current research
results suggest that this mechanism is also of great importance in the progression of heart and kidney diseases.


========================================================================== Story Source: Materials provided by University_of_Bonn. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Andreas Zietzer, Mohammed Rabiul Hosen, Han Wang, Philip Roger
Goody,
Marc Sylvester, Eicke Latz, Georg Nickenig, Nikos Werner, Felix
Jansen.

The RNA-binding protein hnRNPU regulates the sorting of
microRNA-30c-5p into large extracellular vesicles. Journal
of Extracellular Vesicles, 2020; 9 (1): 1786967 DOI:
10.1080/20013078.2020.1786967 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200819094803.htm

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